Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials.

Abstract

Ubrogepant is a small molecular calcitonin gene-related peptide receptor antagonist that is used for the acute treatment of migraine. The aim was to conduct a meta-analysis to systematically evaluate the efficacy and safety of ubrogepant for the treatment of episodic migraine compared with placebo in the adult population. We systematically searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials for relevant randomized clinical trials, from the earliest available date to November 10, 2019, to evaluate the efficacy and safety of short-term ubrogepant use. Inclusion criteria were (1) randomized clinical trial; (2) enrolled adult participants diagnosed with episodic migraine; (3) compared ubrogepant with placebo at doses that were evaluated in phase III clinical trials; (4) enrolled more than 100 patients in each group; and (5) provided any information on primary or secondary outcomes. Trials were excluded if their participants were diagnosed with chronic migraine. A total of three multicenter, randomized clinical trials with 3326 patients were included. Ubrogepant use was associated with a significantly higher percentage of patients with pain freedom (ubrogepant 20.8%; placebo 12.6%; relative risk [RR] 1.65, 95% confidence interval [CI] 1.38-1.98) and absence of the most bothersome migraine-associated symptoms (ubrogepant 37.3%; placebo 27.6%; RR 1.35, 95% CI 1.20-1.53) at 2 h post-dose compared with placebo. Ubrogepant increased the rate of absence of migraine-associated symptoms at 2 h post-dose compared with placebo (photophobia: RR 1.30 [95% CI 1.18-1.44], I2 = 49%; phonophobia: RR 1.20 [95% CI 1.11-1.29]; nausea: RR 1.07 [95% CI 1.02-1.13]), and patients were more likely to function normally at 2 h post-dose compared with placebo (RR 1.30 [95% CI 1.16-1.45]). No significant difference was found for treatment-related adverse events within 48 h or 30 days for ubrogepant compared with placebo (48 h: RR 1.07 [95% CI 0.85-1.35]; 30 days: RR 1.03 [95% CI 0.79-1.34]). Subgroup analysis demonstrated that compared to placebo, ubrogepant led to greater rates of freedom from pain at 2 h with 25-mg, 50-mg, and 100-mg doses and absence of the most bothersome symptoms with 50-mg and 100-mg doses. The use of ubrogepant as an acute treatment of episodic migraine in adults led to a greater percentage of freedom from pain and absence of the most bothersome symptoms at 2 h post-dose. Short-term use of ubrogepant was not related to an increased risk for adverse events. Further studies are needed to evaluate efficacy and safety for long-term use and in specific subgroups of patients.